This is a competing renewal application for a Senior Scientist Award (KO-5) to continue research on the biological and behavioral aspects of substance abuse. The proposed research is based on several awards currently funded by NIDA, NIH. I am Principal Investigator on three awards: (1) a cooperative agreement with NIDA designed to evaluate new strategies for cocaine treatment medications in basic pre-clinical and clinical studies (U19 - DA-11007); (2) an R01 award for pre-clinical studies of the interactions between cocaine and opioid drugs with different receptor selectivities (DA-02519) and (3) a contract concerned with the assessment of potential treatment medications in rhesus monkeys (DA7-8073). I am also Scientific Director of a NIDA Clinical Research Center (P50-DA 04059) involving multi-disciplinary studies of the biological and behavioral consequences of polydrug abuse in women. In addition, I am co-investigator on an R01 award designed to evaluate new medications for the treatment of psychostimulant abuse in clinical studies (DA-10757) and co-investigator on a NIDA training grant (DA- 07252). These interrelated clinical and preclinical multidisciplinary studies focus on two general research areas. One area is concerned with effects of abused substances on the endocrine system with special emphasis on the consequences of drug abuse on reproductive hormones in females as well as assessment of gender differences. The second area is concerned with the evaluation of new medications for drug abuse treatment in clinical studies and in primate models of drug self-administration and drug discrimination. Proposed plans for professional growth include continued study of endocrinology, brain imaging and computer science as well as study of two new directions in our research program that involve collaborative studies in medicinal chemistry and immunology.